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EC number: 201-248-4 | CAS number: 80-08-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Genetic toxicity: in vitro
Administrative data
- Endpoint:
- in vitro gene mutation study in mammalian cells
- Remarks:
- Type of genotoxicity: gene mutation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2000
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 000
- Report date:
- 2000
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: UKEMS Guidelines (1990) and ICH Tripartite Harmonised Guideline on Genotoxicity and ICH Requirements for Registration of Pharmaceuticals for HUman Use, Genotoxicity: a standard battery for genotoxicity testing of pharmaceuticals
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian cell gene mutation assay
Test material
- Reference substance name:
- Dapsone
- EC Number:
- 201-248-4
- EC Name:
- Dapsone
- Cas Number:
- 80-08-0
- Molecular formula:
- C12H12N2O2S
- IUPAC Name:
- 4,4'-sulfonyldianiline
- Details on test material:
- Dapsone, batch no. 70522014, white powder, stored at 1-10 degress C, in the dark.
Source : Sigma Aldrich Co Ltd, Gillingham UK
Constituent 1
Method
- Target gene:
- Thymidine kinase gene
Species / strain
- Species / strain / cell type:
- mouse lymphoma L5178Y cells
- Details on mammalian cell type (if applicable):
- derived from the American Type Culture collection
- Metabolic activation:
- with and without
- Metabolic activation system:
- male Sprague Dawley rats liver enzymes induced with Aroclor 1254
- Test concentrations with justification for top dose:
- Cells were grown in RPMI 10 under 5 % v/v CO2 in the air, 10% Fetal Horse Serum
- Vehicle / solvent:
- DMSO final conc 1 %
Controls
- Untreated negative controls:
- yes
- Negative solvent / vehicle controls:
- yes
- Remarks:
- DMSO
- True negative controls:
- yes
- Positive controls:
- yes
- Details on test system and experimental conditions:
- Expression period was 2 days, cell densitites were adjusted to 10E+4/ml, and samples were dilutes to 8 cells/ml for cell viability.
- Evaluation criteria:
- 1) the acceptance criteria were met
2) the mutant frequency at one or more concentrations was significantly greater than the negative control
3) there was a significant dose-relationship as indicated by the linear trend analysis. - Statistics:
- Statistical significance of mutant frequencies was carried out according to UK UKEMS guidelines Thus the control log frequency was compared with the log mutant frequency from each treatment concentration based on Dunnett's test for multiple comparison and secondly the data were checked for a linear trend in mutant frequencies with treatment concentration using weighted regression.
Results and discussion
Test results
- Species / strain:
- mouse lymphoma L5178Y cells
- Metabolic activation:
- with and without
- Genotoxicity:
- negative
- Cytotoxicity / choice of top concentrations:
- cytotoxicity
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- After 3-hour treatment the cytotoxocicity at 2000 micrograms/ml was too high, so that in the main experiment only 1000 micrograms/ml were tested and evaluates in the absence of S-9.
Thus, in experiment 1, dose levels of 62.5 - 750 microgram/ml were tested without S-9, and 2.5 - 1200 micrograms/ml with S-9.
Any other information on results incl. tables
The positive controls were -nitroquinoline1 -oxide and benzo-a-pyrene.
2 independent experiments were made, using the fluctuation protocol. Both were 3-hour incubation, with a 24-hour incubation.
In the 1st experiment, a survival rate at 1200 micrograms/ml was 20.47 % in absence of S-9 and 51.96% in presence of S-9 at 750 µg/ml.
In the second experiment a survival rate of 33.69% was found in the highest dose level in presence of S-9 (1200 µg/ml).
There was no increase in the mutant frequencies at any dose level, while the positive controls gave results as expected from the historical controls.
Applicant's summary and conclusion
- Conclusions:
- Based on the results in this mammalian gene mutation test on the tk-locus of L5178 Y mouse lymphoma cells, it is concluded that Dapsone is not mutagenic in mammalian cells.
- Executive summary:
Dapsone was assayed for its ability to induce mutation at the tk locus in mouse lymphoma cells using a fluctuation protocol. The study consisted of a cytotoxicity range-finding experiment followed by two independent experiments, in the absence and presence of metabolic activation (rat liver S9).
A 3-hour treatment incubation period was used for all experiments performed in the presence of S9. In the absence of S9, the rangefinder was performed using a 3 hour and 24-hour treatment incubation period, Experiment 1 was performed using a 3 hour treatment incubation and Experiment 2 was performed using a 24 hour treatment incubation.
In the cytotoxicity range-finding experiment, 3-hour treatment, six concentrations were tested, in the absence and presence of S9, with doses ranging from 62.5 to 2000 g/mL (limited by solubility). Extreme toxicity was observed at the top concentration tested, both with and without metabolic activation. The maximum concentration where cells survived treatment was 1000 g/mL, with a 5.79% and 14.47% relative survival in the absence and presence of S9 respectively.
In the 24h range finding experiment, nine concentrations were chosen in the absence of S9, with concentrations up to 2000 g/mL. Extreme toxicity was observed at the top two concentrations tested (1000 and 2000 g/mL), the top concentration where cells survived was 500 g/mL, which yielded 10.14% relative survival.
Accordingly, for the first experiment, six concentrations were chosen without S9, upto 750 g/mL and seven concentrations were chosen in the presence of S9, upto 1200 g/mL. Two days post treatment, all concentrations were selected to determine viability and TFT resistance. The top concentrations tested were 75 and 1200 g/mL, which yielded 51.96 % (absent of S9) and 20.47% (with S9).
In the second experiment, seven concentrations were tested in the absence of s9, ranging from 31.25 to 750 g/mL and seven concentrations were tested in the presence of S9 (3h) ranging from 62.5 to 1200 g/mL. Two days after the end of treatment all concentrations tested in the absence and presence of S9 were selected to determine TFT resistance. However, the top concentration tested in the absence of S9 (750 g/mL), was later rejected from analysis due to excessive heterogeneity. This concentration was also highly toxic, yielding less than 10% relative survival. The top concentrations analyzed were 500 g/mL in the absence of S9 and 1200 g/mL in the presence of, which yielded 27.69% and 33.69% relative survival respectively. The top concentration in all experiments was limited by test article solubility in tissue culture medium.
No statistically significant increase in mutant frequency was observed following treatment with dapsone at any concentration level tested, in the absence or presence of S9. Dapsone was not considered mutagenic in this test system.
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